The present invention relates to the preparation of pyrocarbonic acid diesters by an improved process and to the novel pyrocarbonic acid diesters prepared according to said process as well as to the use thereof. The products are obtained in high yield and are of very high purity.
Pyrocarbonic acid diesters themselves are active compounds and are used, for example, as antiseptic agents for food. In addition, specific pyrocarbonic acid diesters, such as di-tert-butyl dicarbonate (DIBOC), are important fine chemicals, e.g. for introducing protective groups such as carbonate into alcohols, thiocarbonate into thiols or, in particular, urethane into amines or amides. Such groups are distinguished in that they are stable under normal conditions but can nevertheless be separated, for example hydrolytically or thermally, with reconversion of the original functions.
Substances which utilise said properties for technical purposes are known from EP 648 770 and EP 648 817. However, in contradistinction to standard tert-butyl urethanes prepared from DIBOC, more precise demands are made in such cases on the properties, in particular on the thermal properties. There is therefore a need for novel pyrocarbonic acid diesters as synthesis building blocks.
In view of the importance as food additives and fine chemicals, the most stringent demands are made on DIBOC and other dicarbonates with respect to purity. Many efforts have therefore been made to prepare DIBOC in ever enhanced quality and yield. This is complicated by DIBOC being thermally instable, as is indicated in J. Org. Chem. 43, 2410 (1978).
DIBOC can be prepared by two fundamentally different processes. In the first process, which is described in Org. Synth. 57, 45 (1975) and JP-88/051358, tert-butyl carbonate is reacted with phosgene to di-tert-butyl tricarbonate which is then decarboxylated in the presence of a tertiary amine (for example 1,4-diazabicyclo[2.2.2]octane) as catalyst, according to JP-91/356445 preferably with the addition of a phase transfer catalyst. In JP-92/310646, the tertiary amine is pyridine in a non-specific amount. According to JP-89/186847 it is also possible to use thionyl chloride instead of phosgene.
In the second, and generally preferred, process according to Zh. Org. Khim. 15/1, 106 (1975), tert-butyl carbonate is reacted with an acid chloride to a mixed carboxylic acid anhydride which is converted into the desired dicarbonate with excess tert-butyl carbonate. This process can be improved by replacing carboxylic anhydrides with sulfochlorides (CS-247845 and CS-247846). Other measures for the improvement of this process have also been proposed, for example the addition of a quaternary ammonium salt (CS-257157), the use of amines with an aliphatically bonded tertiary nitrogen, typically triethylamine, N,N-dimethylbenzylamine or N,N,Nxe2x80x2,Nxe2x80x2-tetramethylethylenediamine (JP-90/103562), concentrating free sodium hydroxide solution below 10 mol % (JP-92/194326) or concentrating free sodium alcoholate below 3 mol % (JP-92/310648), the use of carbon dioxide under pressure (JP-92/279301) as well as the salt-free washing of the crude product prior to distilliation (JP-92/306261).
It has been found, however, that in spite of improvements all processes described above are still not entirely satisfactory. High yields, for example, are only achieved at elevated temperature, by prolonged reaction times or in the presence of considerable amounts of polar hydrophilic solvents such as tetrahydrofuran or dimethylformamide. Such polar hydrophilic solvents, however, which are used in pure or mixed form, cannot be readily recovered, if at all, and residues can enter into the waste water during washing. These processes therefore entail great ecological problems which can only be solved satisfactorily with considerable expenditure of costs. In addition, the quality of the crude products obtained leaves much to be desired, requiring a particularly careful and time-consuming fractional distillation to isolate the pure product. However, owing to the thermal sensitivity of DIBOC, distillation should, if possible, be avoided altogether or be at least carried out very rapidly, for example in a single step falling film evaporator.
CS-260076 proposes carrying out this process in the presence of pyridine and a quaternary ammonium salt. While this permits a reaction at room temperature, the yield is only 38.6% of theory and therefore an elevated temperature of preferably 50xc2x0 C. is indicated in order to improve the yield. It has been found, however, that this induces the decomposition of the product and that said product contains considerable amounts of unreacted p-toluene sulfochloride, so that this method does not solve the problems described above.
EP 468 404 therefore proposes to replace tosyl chloride with mesyl chloride to improve the reactivity. This process should make it possible to produce good product qualities according to the description and the yield could even be increased by adding phase transfer catalysts, aromatic amines, or mixtures thereof.
In practice, however, it has been found that this latter process is also problematical. It has been found, for example, that very vigorous stirring of the reaction mixture is absolutely essential, which in laboratory practice is only possible with a special stirrer, and the yields decrease drastically in the scale-up. This problem is apparently caused at least partly by the physical properties of mesyl chloride which is a liquid of high specific density. In addition, mesyl chloride has a relatively high vapour pressure and is very caustic; it hydrolyses easily and reacts also with the alcoholate to be reacted under formation of methane sulfonic acid alkyl esters, which have a boiling point similar to that of the desired pyrocarbonic acid diesters so that their traces can hardly be removed at all by distillation. Because of this undesirable side reaction, mesyl chloride is also sometimes used in slight excess. And, finally, the resulting methane sulfonic acid cannot be isolated from the aqueous solution for recycling as easily as might be desired.
Surprisingly, it has now been found that pyrocarbonic acid diesters can in fact be obtained from ester carbonate and tosyl chloride in excellent yield and purity if this reaction is carried out in the presence of an ammonium salt and very small amounts of pyridine in a nonpolar inert solvent. Tosyl chloride and pyridine can also be replaced with structurally similar compounds, giving comparable results.
Accordingly, the invention relates to a process for the preparation of a pyrocarbonic acid diester of formula (I) 
wherein R1 and R1xe2x80x2 are each independently of the other branched or straight-chain C1-C24alkyl, C3-C24alkenyl, C3-C24alkynyl, C4-C12cycloalkyl, C4-C12cycloalkenyl or C7-C24aralkyl, each of which is unsubstituted or substituted by one or more than one substituent which is inert under the reaction conditions,
by reacting at least one ester carbonate of formula (II) 
wherein M+ is Na+, Li+, K+ or NR2R3R4R5+, and R2 to R5 are each independently of one another hydrogen, C1-C18alkyl, C5-C10cycloalkyl or C7-C18aralkyl,
xe2x80x83with 40-50 mol % of a sulfochloride of formula (IV) 
wherein R6 is xe2x80x94H, xe2x80x94CH3, xe2x80x94CH2CH3, xe2x80x94Cl, xe2x80x94Br, xe2x80x94OCH3 or xe2x80x94NO2,
xe2x80x83in the presence of 0.8-5 mol % of a catalyst of formula (V) 
xe2x80x83wherein
R2 to R5 have the meaning cited above, and
Xxe2x88x92 is a non-nucleophilic anion,
and with minor amounts of a heterocyclic aromatic amine in a nonpolar inert solvent,
in which process the amount of heterocyclic aromatic amine is 1-5 mol % and the reaction is carried out in the temperature range from xe2x88x9210xc2x0 C. to +25xc2x0 C.,
all molar amounts being based on 100 mol % of ester carbonate of formula (II).
C1-C18Alkyl is typically methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2,2-dimethylpropyl, n-hexyl, n-octyl, 1,1,3,3-tetra-methylbutyl, 2-ethylhexyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl or octadecyl. C1-C24Alkyl can additionally be, for example, eicosyl, heneicosyl, docosyl or tetracosyl.
C3-C24Alkenyl is C3-C24alkyl which is mono- or polyunsaturated and wherein two or more than two double bonds can be isolated or conjugated, for example allyl, 2-propen-2-yl, 2-buten-1-yl, 3-buten-1-yl, 1,3-butadien-2-yl, 2-penten-1-yl, 3-penten-2-yl, 2-methyl-1-buten-3-yl, 2-methyl-3-buten-2-yl, 3-methyl-2-buten-1-yl, 1,4-pentadien-3-yl, or the different isomers of hexenyl, octenyl, nonenyl, decenyl, dodecenyl, tetradecenyl, hexadecenyl, octadecenyl, eicosenyl, heneicosenyl, docosenyl, tetracosenyl, hexadienyl, octadienyl, nonadienyl, decadienyl, dodecadienyl, tetradecadienyl, hexadecadienyl, octadecadienyl, eicosadienyl, heneicosadienyl, docosadienyl or tetracosadienyl.
C4-C12Cycloalkyl is, for example, a monocyclic cycloalkyl, typically cyclobutyl, cyclopentyl, cyclohexyl, trimethylcyclohexyl or menthyl, or a polycyclic cycloalkyl, typically thujyl, bornyl, 1-adamantyl or 2-adamantyl.
C4-C12Cycloalkenyl is C4-C12cycloalkyl which is mono- or polyunsatured and wherein two or more than two double bonds can be isolated or conjugated, typically 2-cyclobuten-1-yl, 2-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-cyclohexen-1-yl, 2,4-cyclohexadien-1-yl, 1-p-menthen-8-yl, 4(10)-thujen-10-yl, 2-norbornen-1-yl, 2,5-norbornadien-1-yl or 7,7-dimethyl-2,4-norcaradien-3-yl.
C3-C24Alkynyl is C3-C24alkyl or C3-C24alkenyl, each of which is once or more than once doubly unsaturated and wherein the triple bonds can be isolated or conjugated among themselves or with double bonds, typically 1-propin-3-yl, 1-butin-4-yl, 1-pentin-5-yl, 2-methyl-3-butin-2-yl, 1,4-pentadiin-3-yl, 1,3-pentadiin-5-yl, 1-hexin-6-yl, cis-3-methyl-2-penten-4-in-1-yl, trans-3-methyl-2-penten-4-in-1-yl, 1,3-hexadiin-5-yl, 1-octin-8-yl, 1-nonin-9-yl, 1-decin-10-yl or 1-tetracosin-24-yl.
C7-C18Aralkyl is typically 2-benzyl-2-propyl, xcex2-phenylethyl, xcex1,xcex1-dimethylbenzyl, xcfx89-phenyl-butyl, xcfx89-phenyloctyl, xcfx89-pentyldodecyl or 3-methyl-5-(1xe2x80x2,1xe2x80x2,3xe2x80x2,3xe2x80x2-tetramethyl)butylbenzyl. C7-C24Aralkyl can additionally be, for example, 2,4,6-tri-tert-butylbenzyl or 1-(3,5-dibenzyl-phenyl)-3-methyl-2-propyl.
If R1 and R1xe2x80x2 are substituted, then the substituents can be such that they are inert under the reaction conditions. Typical examples of inert substituents are halogen atoms, for example fluoro or chloro, ether groups, such as xe2x80x94Oxe2x80x94R2 or xe2x80x94(Oxe2x80x94C1-C6)nxe2x80x94Oxe2x80x94C1-C18alkyl, typically methoxy, ethoxy, butoxy, octadecyloxy, 3-oxahept-1-yloxy, or monomethoxy polyethylene radicals, monoethoxy polyethylene glycol radicals, monomethoxy polypropylene glycol radicals or monoethoxy polypropylene radicals, amino groups, such as xe2x80x94NR2R3, typically dimethylamino, methylethylamino, diethylamino, dibutylamino, butyldodecylamino, dioctadecylamino or methyl(3-aza-hept-1-yl)amino, thioether groups, such as xe2x80x94Sxe2x80x94R2 (R2xe2x89xa0H), typically methylthio, ethylthio, butylthio or octadecylylthio, cyano, nitro or xcex1,xcex2-unsaturated ketone radicals. Known pyrocarbonic acid diesters of formula (I), wherein R1 and R1xe2x80x2 carry inert substituents, are e.g. di(1,1,1,3,3,3-hexafluoro-2-propyl)dicarbonate or di[1-methyl-3-(2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-2-propenyl]dicarbonate.
Heterocyclic aromatic amines are, for example, pyridine, xcex1-, xcex2- or xcex3-picoline, 2,4-, 2,6-, 3,4- or 3,5-lutidine, collidine or quinoline.
Nonpolar inert solvents are those having a dielectric constant ∈xe2x89xa610 and which are immiscible with water and which, under the conditions of this process, react neither with the ester carbonate of formula (II) nor with the sulfochloride of formula (IV), for example aromatic hydrocarbons, typically benzene, toluene, xylene, mesitylene or ethylbenzene, aliphatic hydrocarbons, typically pentane, hexane, cyclohexane, heptane, octane, decane or decahydronaphthalene, noncyclic ethers, typically diethyl ether, diisopropyl ether, diisopropyl ether or diisobutyl ether, or mixtures thereof, for example special boiling-point spirit or (copyright)Shell-Sol products.
Sulfochlorides of formula (IV) are preferably benzene sulfochloride and p-toluene sulfochloride.
Preferred catalyst cations are those wherein R2 to R5 are each independently of one another methyl, ethyl, butyl, benzyl, octyl, dodecyl or octadecyl, in particular those wherein the sum of the carbon atoms in the groups R41 to R44 is from 10 to 24.
Particularly preferred catalyst cations are those wherein R2 to R5 are butyl, or R2 and R3 are methyl, R4 is methyl or ethyl, and R5 is benzyl, dodecyl or octadecyl.
Non-nucleophilic catalyst anions Yxe2x88x92 are typically Clxe2x88x92, Brxe2x88x92, Fxe2x88x92, Jxe2x88x92, NO3xe2x88x92, ClO4xe2x88x92, HSO4xe2x88x92, PF6xe2x88x92, B(C6H5)4xe2x88x92 or BF4xe2x88x92.
Catalyst anions are preferably bromide and chloride, in particular chloride.
A particularly preferred catalyst of formula (V) is benzyltrimethylammonium chloride.
Heterocyclic aromatic amine is preferably pyridine.
Solvents are preferably aromatic hydrocarbons.
Particularly preferred solvents are toluene and xylene.
The preferred amount of sulfochloride of formula (IV) is c. 45 mol %, based on (II).
The preferred amount of catalyst of formula (V) is 1.0-1.5 mol %, based on (II).
The preferred amount of heterocyclic aromatic amine is 1-3 mol %, based on (II). The particularly preferred amount of heterocyclic aromatic amine is c. 3 mol %, based on (II). The amount of solvent is not critical. It is preferred to use exactly the amount of solvent required to make the reaction mixture readily stirrable during the entire reaction, which amount can differ depending on the pyrocarbonic acid diester to be prepared. The reaction temperature is preferably from 0xc2x0 C. to +20xc2x0 C.
The reaction temperature is particularly preferably from 0xc2x0 C. to +10xc2x0 C.
The reaction time depends on the amounts of catalyst and heterocyclic aromatic amine as well as on the temperature. The reaction is usually completed after xc2xd to 100 hours, preferably after xc2xd to 10 hours.
All the chemicals required are known and are commercially available or can be prepared according to known methods.
The process can be carried out most simply by introducing the solvent and all educts (II) to (V) concurrently or in succession and in any order into the reaction vessel at the reaction temperature. Conveniently, at least part of the solvent is placed in the reaction vessel first and the sulfochloride is added last.
The ester carbonate of formula (II) is preferably prepared in situ according to known processes, for example as indicated in the above literature references. In this process, an alcoholate of formula (VI) 
is added to a solvent, which may also be done by reacting an alcohol R1OH with an alkali metal M or an alkali metal hydride MH in the above solvent in an inert atmosphere. Carbon dioxide is then introduced, where appropriate under pressure, until the ester carbonate of formula (II) is formed. It may be expedient to deviate from the temperature range for the preparation of the pyrocarbonic acid diester. In particular, elevated temperatures, e.g. reflux temperature, are suitable to accelerate and complete the alcoholate formation from alcohol and metal, and lower temperatures, e.g. xe2x88x9215xc2x0 C., are suitable to moderate the alcoholate formation from alcohol and metal hydride.
To the solution or suspension of the ester carbonate of formula (II) are then added, with stirring, the catalyst of formula (V), the heterocyclic aromatic amine and the sulfochloride of formula (IV) in the amounts indicated above at the specified reaction temperature from xe2x88x9210xc2x0 C. to +25xc2x0 C. If required, the reaction can be observed using gas chromatography.
The reaction mixture can subsequently also be processed in standard manner, typically by washing with dilute aqueous acid and/or with water and by concentrating the separated organic phase by evaporation. Prior to being concentrated by evaporation, the organic phase can be treated with customary known agents, typically drying agents such as anhydrous sodium sulfate or magnesium sulfate, or adsorbents, such as activated carbon or bleaching earths.
The pyrocarbonic acid diesters of formula (I) are obtained in high yield and purity. If desired, they can additionally be distilled, and because of the high purity of the crude product the distillation can be carried out particularly gently and rapidly.
Owing to the improved reactivity achieved by this invention it is possible to use amounts of sulfochloride up to near the stoichiometrically determined limit of 50 mol % without any contamination of the product with unreacted sulfochloride and without any substantial prolongation of the reaction time. A preferred amount of sulfochloride is c. 45 mol %, based on 100 mol % of ester carbonate of formula (II).
Using mixtures of ester carbonates. of formula (II), asymmetrical pyrocarbonic acid diesters of formula (I) can be obtained, wherein R1 and R1xe2x80x2 are different. In this case it is expedient to use a molar ratio of 1:1, one ester carbonate preferably being added first and the other ester carbonate being added only after the sulfochloride. Depending on the end use requirement, such pyrocarbonic acid diesters can be used as mixtures of homologues, or the asymmetrical compound can be isolated, for example by fractional distillation.
Known pyrocarbonic acid diesters are those of formulae (VI) 
wherein R7 as well as R7xe2x80x2 are C1-C24alkyl which is not branched in a-position and which is unsubstituted or substituted by one or more than one substituent which is inert under the reaction conditions, and (VII) 
xe2x80x83wherein
R1 is as defined above, and R8 is branched or straight-chain C3-C24alkenyl, C3-C24alkynyl, C4-C12cycloalkyl, C4-C12cycloalkenyl or C7-C24aralkyl, each of which is unsubstituted or substituted by one or more than one substituent which is inert under the reaction conditions,
or C7-C24alkyl which is branched in xcex1-position,
R1 and R8 in formula (VII) being combined as indicated in Table 1:
The other pyrocarbonic acid diesters of formula (I) which can be prepared according to the process of this invention are still novel.
Accordingly, the invention also relates to pyrocarbonic acid diesters of formula (VIII) 
wherein
R9 is branched or straight-chain C1-C24alkyl, C3-C24alkenyl, C3-C24alkynyl, C4-C12cycloalkyl, C4-C12cycloalkenyl or C7-C24aralkyl, each of which is unsubstituted or substituted by one or more than one substituent which is inert under the reaction conditions, and
R10 is independently of R9 branched or straight-chain C3-C24alkenyl, C3-C24alkynyl, C4-C12cycloalkyl, C4-C12cycloalkenyl or C7-C24aralkyl, each of which is unsubstituted or substituted by one or more than one substituent which is inert under the reaction conditions,
or C3-C24alkyl which is branched in xcex1-position,
with the proviso that it is not possible that R9 is R1 and R10 is R8 at the same time,
wherein R1 and R8 have the meaning indicated in Table 1.
Preferred pyrocarbonic acid diesters are those of formula (I), wherein R1 and R1xe2x80x2 are attached at the oxygen atom of the dicarbonate group with a secondary or tertiary carbon atom, as well as those wherein R1 and R1xe2x80x2 are unsaturated in xcex2-position, in particular di-tert-butyl dicarbonate, di-tert-pentyl dicarbonate, di-5-nonyl dicarbonate, diallyl dicarbonate, di(2-methyl-3-butin-2-yl) dicarbonate or di(2-methyl-3-buten-2-yl) dicarbonate.
Particularly preferred pyrocarbonic acid diesters of formula (I) are di-tert-pentyl dicarbonate, di-5-nonyl dicarbonate, diallyl dicarbonate, di(2-methyl-3-buten-2-yl) dicarbonate or di(2-methyl-3-butin-2-yl) dicarbonate.
The pyrocarbonic acid diesters of formula (VIII) can be used for any known purpose and can be preferably used for the preparation of soluble pigment precursors, such as those disclosed in EP 648 770 and EP 648 817.
Preferred pigment precursors for the preparation of which pyrocarbonic acid diesters of formula (VIII) can be used, are those of formula (IX)
A(B)xxe2x80x83xe2x80x83(IX),
wherein
x is an integer from 1 to 4,
A is the radical of a chromophore of the quinacridone, anthraquinone, indanthrone, perylene, indigo, quinophthalone, isoindolinone, isoindoline, dioxazine, azo, phthalocyanine or diketopyrrolopyrrole series, which radical A contains x N-atoms which are conjugated with, or adjacent to, at least one carbonyl group, and
B is a group of formula (X) 
which is linked to one of these N-atoms and wherein R9 has the meaning cited above.
The chromophore radicals and substitution patterns of such pigment precursors, as well as pigment precursors themselves, are known from, inter alia, EP 654 711.